 |
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
Presynaptic neurotoxin
|
PDB id
|
|
|
|
1omg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
 |
|
 |
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
 |
 |
 |
|
 |
 |
 |
 |
|
 |
|
Cellular component
|
extracellular region
|
1 term
|
 |
|
Biological process
|
pathogenesis
|
1 term
|
 |
|
Biochemical function
|
ion channel inhibitor activity
|
1 term
|
 |
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
| |
|
DOI no:
|
Biochemistry
34:10256-10265
(1995)
|
|
PubMed id:
|
|
|
|
|
| |
|
Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin MVIIA.
|
|
T.Kohno,
J.I.Kim,
K.Kobayashi,
Y.Kodera,
T.Maeda,
K.Sato.
|
|
|
|
| |
ABSTRACT
|
|
|
| |
|
The three-dimensional solution structure of omega-conotoxin MVIIA, a 25-mer
peptide antagonist of N-type calcium channels, was determined by two-dimensional
1H NMR spectroscopy with simulated annealing calculations. A total of 13
converged structures of omega-conotoxin MVIIA were obtained on the basis of 273
experimental constraints, including 232 distance constraints obtained from
nuclear Overhauser effect (NOE) connectivities, 22 torsion angle (phi, chi 1)
constraints, and 19 constraints associated with hydrogen bonds and disulfide
bonds. The atomic root mean square difference about the averaged coordinate
positions is 0.47 +/- 0.08 A for the backbone atoms (N, C alpha, C) and 1.27 +/-
0.14 A for all heavy atoms of the entire peptide. The molecular structure of
omega-conotoxin MVIIA is composed of a short triple-stranded antiparallel
beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as
that reported for omega-conotoxin GVIA, another N-type calcium channel blocker.
The orientation of beta-stranded structure is similar to each other, suggesting
that the conserved disulfide bond combination is essential for the molecular
folding. We have recently determined by using alanine substitution analyses that
Tyr 13 is essential for the activity of both toxins. On the basis of functional
and structural analysis, it is shown that both omega-conotoxin MVIIA and GVIA
retain a similar conformation to locate Tyr 13 in the appropriate position to
allow binding to N-type calcium channels. These results provide a molecular
basis for understanding the mechanism of calcium channel modulation through the
toxin-channel interaction and insight into the discrimination of different
subtypes of calcium channels.
|
|
|
|
|
|
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
H.Kolmar
(2008).
Alternative binding proteins: biological activity and therapeutic potential of cystine-knot miniproteins.
|
| |
FEBS J, 275,
2684-2690.
|
 |
|
|
|
|
 |
J.G.McGivern
(2007).
Ziconotide: a review of its pharmacology and use in the treatment of pain.
|
| |
Neuropsychiatr Dis Treat, 3,
69-85.
|
 |
|
|
|
|
 |
D.P.Wermeling
(2005).
Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain.
|
| |
Pharmacotherapy, 25,
1084-1094.
|
 |
|
|
|
|
 |
R.Krätzner,
J.E.Debreczeni,
T.Pape,
T.R.Schneider,
A.Wentzel,
H.Kolmar,
G.M.Sheldrick,
and
I.Uson
(2005).
Structure of Ecballium elaterium trypsin inhibitor II (EETI-II): a rigid molecular scaffold.
|
| |
Acta Crystallogr D Biol Crystallogr, 61,
1255-1262.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
C.Bernard,
G.Corzo,
S.Adachi-Akahane,
G.Foures,
K.Kanemaru,
Y.Furukawa,
T.Nakajima,
and
H.Darbon
(2004).
Solution structure of ADO1, a toxin extracted from the saliva of the assassin bug, Agriosphodrus dohrni.
|
| |
Proteins, 54,
195-205.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
H.W.Tedford,
N.Gilles,
A.Ménez,
C.J.Doering,
G.W.Zamponi,
and
G.F.King
(2004).
Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against insect calcium channels.
|
| |
J Biol Chem, 279,
44133-44140.
|
 |
|
|
|
|
 |
L.Volpon,
H.Lamthanh,
J.Barbier,
N.Gilles,
J.Molgó,
A.Ménez,
and
J.M.Lancelin
(2004).
NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels.
|
| |
J Biol Chem, 279,
21356-21366.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
Z.P.Feng,
C.J.Doering,
R.J.Winkfein,
A.M.Beedle,
J.D.Spafford,
and
G.W.Zamponi
(2003).
Determinants of inhibition of transiently expressed voltage-gated calcium channels by omega-conotoxins GVIA and MVIIA.
|
| |
J Biol Chem, 278,
20171-20178.
|
 |
|
|
|
|
 |
D.P.Goldenberg,
R.E.Koehn,
D.E.Gilbert,
and
G.Wagner
(2001).
Solution structure and backbone dynamics of an omega-conotoxin precursor.
|
| |
Protein Sci, 10,
538-550.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
S.Ludvigsen,
L.Thim,
A.M.Blom,
and
B.S.Wulff
(2001).
Solution structure of the satiety factor, CART, reveals new functionality of a well-known fold.
|
| |
Biochemistry, 40,
9082-9088.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
K.J.Nielsen,
T.Schroeder,
and
R.Lewis
(2000).
Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels.
|
| |
J Mol Recognit, 13,
55-70.
|
 |
|
|
|
|
 |
K.Kobayashi,
T.Sasaki,
K.Sato,
and
T.Kohno
(2000).
Three-dimensional solution structure of omega-conotoxin TxVII, an L-type calcium channel blocker.
|
| |
Biochemistry, 39,
14761-14767.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
R.A.Atkinson,
B.Kieffer,
A.Dejaegere,
F.Sirockin,
and
J.F.Lefèvre
(2000).
Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange.
|
| |
Biochemistry, 39,
3908-3919.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
S.Menzler,
J.A.Bikker,
N.Suman-Chauhan,
and
D.C.Horwell
(2000).
Design and biological evaluation of non-peptide analogues of omega-conotoxin MVIIA.
|
| |
Bioorg Med Chem Lett, 10,
345-347.
|
 |
|
|
|
|
 |
A.Wentzel,
A.Christmann,
R.Krätzner,
and
H.Kolmar
(1999).
Sequence requirements of the GPNG beta-turn of the Ecballium elaterium trypsin inhibitor II explored by combinatorial library screening.
|
| |
J Biol Chem, 274,
21037-21043.
|
 |
|
|
|
|
 |
B.Gilquin,
A.Lecoq,
F.Desné,
M.Guenneugues,
S.Zinn-Justin,
and
A.Ménez
(1999).
Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine.
|
| |
Proteins, 34,
520-532.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
K.J.Nielsen,
D.A.Adams,
P.F.Alewood,
R.J.Lewis,
L.Thomas,
T.Schroeder,
and
D.J.Craik
(1999).
Effects of chirality at Tyr13 on the structure-activity relationships of omega-conotoxins from Conus magus.
|
| |
Biochemistry, 38,
6741-6751.
|
 |
|
|
|
|
 |
M.Price-Carter,
M.S.Hull,
and
D.P.Goldenberg
(1998).
Roles of individual disulfide bonds in the stability and folding of an omega-conotoxin.
|
| |
Biochemistry, 37,
9851-9861.
|
 |
|
|
|
|
 |
P.Savarin,
M.Guenneugues,
B.Gilquin,
H.Lamthanh,
S.Gasparini,
S.Zinn-Justin,
and
A.Ménez
(1998).
Three-dimensional structure of kappa-conotoxin PVIIA, a novel potassium channel-blocking toxin from cone snails.
|
| |
Biochemistry, 37,
5407-5416.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
A.C.Rigby,
J.D.Baleja,
B.C.Furie,
and
B.Furie
(1997).
Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer.
|
| |
Biochemistry, 36,
6906-6914.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
J.I.Fletcher,
R.Smith,
S.I.O'Donoghue,
M.Nilges,
M.Connor,
M.E.Howden,
M.J.Christie,
and
G.F.King
(1997).
The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider.
|
| |
Nat Struct Biol, 4,
559-566.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
K.H.Han,
K.J.Hwang,
S.M.Kim,
S.K.Kim,
W.R.Gray,
B.M.Olivera,
J.Rivier,
and
K.J.Shon
(1997).
NMR structure determination of a novel conotoxin, [Pro 7,13] alpha A-conotoxin PIVA.
|
| |
Biochemistry, 36,
1669-1677.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
M.Price-Carter,
W.R.Gray,
and
D.P.Goldenberg
(1996).
Folding of omega-conotoxins. 1. Efficient disulfide-coupled folding of mature sequences in vitro.
|
| |
Biochemistry, 35,
15537-15546.
|
 |
|
|
|
|
 |
M.Price-Carter,
W.R.Gray,
and
D.P.Goldenberg
(1996).
Folding of omega-conotoxins. 2. Influence of precursor sequences and protein disulfide isomerase.
|
| |
Biochemistry, 35,
15547-15557.
|
 |
|
 |
 |
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|